Although small animal models have been found indispensable in medical research, their potential has not been fully explored yet, because of a current limitation that the animals have to be sacrificed for analysis. This prevents researchers from observing in vivo the natural or perturbed physiological/pathological processes in a noninvasive and repeatable fashion. Tomographic imaging is the only approach for providing multi-dimensional data about biochemical, genetic or pharmacological processes in vivo. Therefore, NCI initiated the Small Animal Imaging Resource Programs.
Neoplasms have an intrinsic spatially distributed nature. Typically, tumors develop in different sites, metastasize to other sites and are internally heterogeneous. To reveal the characteristics of tumors, spatially distributed and temporally varied measurements need to be taken, preferably with contrast enhancement. Imaging is a key resource for studying the development, growth and therapeutic response of neoplasms, especially in the oncologic settings. It is well known that administration of a contrast material provides a short temporal window for optimally imaging the vasculature, lesions and tumors. Contrast enhancement imaging becomes increasingly important for functional studies of lesions and tumors. Analysis of volumetric and dynamic images of small animals will lead the way to application of quantitative methods in human beings.
Over the past several years, tremendous progress has been made in X-ray detector techniques, real-time/volumetric CT algorithms, and computing resources. Development of a volumetric CT fluoroscopy (VCTF) system for small animal studies has just become commercially feasible. It would be desirable to make volumetric CT fluoroscopy a vital tool in biomedical laboratories for various applications, especially small animal studies, such as contrast-enhancement dynamic imaging for diagnosis and treatment of tumors.
Currently, small animal imaging systems are rarely available, which severely restricts studies of tumors in model systems. Most biomedical imaging devices have been tuned for human studies and have suboptimal performance for small animal studies and their tumors. Therefore, it is desirable to scale down imaging systems for significantly improved images of mouse-sized objects. Micro-CT systems have been proved useful for studying bony structures, solid organs and soft tissues. With contrast enhancement, micro-CT allows 3D-motion analysis and functional imaging. Because of its unique imaging capabilities and relatively low cost, micro-CT has been established as a unique imaging modality for small animal studies in cancer research.
In 1987, Flannery et al. applied the 2D CCD array technology in micro-CT. In the 1990s, a number of micro-CT systems were constructed. Most of these systems employ CCD cameras, micro-focus x-ray tubes, and have image resolutions between 20-100 xcexcm. A major application of micro-CT scanners is small animal imaging. In recent prototypes of such systems, the data acquisition system rotates about an animal table, while in earlier systems an animal stage is rotated in a fixed data acquisition system These imaging systems permit screening of small animals for mutations or pathologies and monitoring of disease progression and response to therapy. A state-of-the-art micro-CT scanner for small animal imaging was developed by Paulus et al. at the Oak Ridge National Laboratory. Their scanner was demonstrated to be effective for detection and characterization of soft-tissue structures, skeletal abnormalities, and tumors in live animals. The scanner allows rapid data acquisition (5-30 minutes) and provides high-resolution images ( less than 50 xcexcm).
A system known as the Dynamic Spatial Reconstructor (DSR) was developed at Mayo Clinic [Ritman et al., 1985]. In the DSR, 28 X-ray tubes are arranged in a semicircle in a circular gantry. Projections formed on the fluorescent screen arc, scanned via multiple imaging chains, and reconstructed volumetrically. Nevertheless, the DSR suffers from a number of drawings, including its complexity and high cost.
A cone-beam X-ray microtomographic imaging systems has been developed [Pan et al., 1998]. This microtomographic imaging system consists of a conventional dental X-ray source (Astech 65), a sample translation and rotation stage, and X-ray scintillation phosphor screen, and a high resolution slow scan cooled CCD camera (Kodak KAF 1400). An epoxy embedded human inner ear specimen was studied using this system [Pan et al., 1998]. The source-to-detector distance and the specimen-to-detector distance were 70 mm and 11 mm, respectively. One hundred equal angular projections were captured by the CCD camera with a 12 bit dynamic range and 1317xc3x97967 detectors covering 30xc3x9722 mm2 on the phosphor screen. Each projection was integrated over 0.16 second, and normalized against the background. Volumetric images have been successfully reconstructed [Wang et al., 1993; Pan et al., 1998].
The present invention relates to a system for use in small animal studies and other applications that include a volumetric CT fluoroscopy (VCTF) scanner and operates in accordance with a novel method that draws from the Feldkamp algorithm The VCTF system is a significant advancement of micro-CT techniques known in the prior art, and has important and immediate applications for small animal studies. While prior micro-CT systems are featured by relatively slow data acquisition and static image reconstructions, the present invention includes real-time data acquisition hardware, a dedicated real-time image reconstruction algorithm, and an extra-fast cone-beam reconstruction engine, and integrating them into a 4D micro-CT scanner.
The system of the present invention can be constructed relatively economically using state-of-the-art source and CCD techniques. Novel image reconstruction methods improve upon prior systems, such as the DSR.